Clinical research in cell disease (SCD) has reached a new developmental milestone. Ironically, the recent success of hydroxyurea and other new treatments makes the work of clinical investigation harder. In order to move the field forward, we now need to develop clinical investigators who excel in the arenas of clinical investigation and sickle cell disease. Dr. Brigitta U. Mueller is an ideal person to grow into this role. She is a pediatric hematologist/oncologist who early on focused on clinical trials related to pediatric HIV disease at the National Cancer Institute's (NCI) intramural program. We have recruited her to Children's Hospital so that she can shift her attention to sickle cell disease while expanding her training and experience in clinical investigation. The goal of our five-year development plan is for her to become an independent investigator - lead sickle cell clinical research at our institution, and direct multi-institutional studies. Dr. Mueller will pursue her career development under the mentorship of Dr. Orah S. Platt, an experienced investigator in sickle cell disease, and Dr. Carlo Brugnara, an expert in design of innovative therapies in sickle cell disease. She will focus her efforts in four major areas: 1) Throughout the 5 years she will see and discuss patients with Dr. Platt, and meet with Dr. Brugnara to discuss research ideas and review data. 2) She will conduct and analyze the proposed clinical trial - evaluating the effect of Mg, a known inhibitor of K-Cl cotransport, in patients with Hb SC disease. Our hypothesis is that oral Mg will block K- Cl cotransport, prevent cell dehydration, and reduce polymerization-induced vasoocclusive complications. 3) She will design and implement a research infrastructure that will be used as a resource for future proposals. 4) She will do course work at the Harvard School of Public Health and obtain the MPH degree, concentrating on research design, implementation; and analysis. The trial of Mg for the prevention of pain crises in patients with Hb SC disease that we propose, will serve as a template for bringing a variety of treatments designed in basic laboratories to clinical trial.